The Complex Role of Anticoagulation in Cirrhosis: An Updated Review of Where We Are and Where We Are Going.

Venous thromboembolism (VTE) in cirrhotic patients is an increasingly encountered problem in the daily clinical practice; there is still a debate on the ideal measures to be followed for prophylaxis and treatment of VTE among this population. Although traditionally, liver cirrhosis has been considered a disease with hypocoagulability state and increasing bleeding tendency due to severe homeostatic disruption in liver disease, until recently there is increasing awareness and evidence that cirrhotic patients are not completely protected from thrombotic events although they have an elevated international normalized ratio and auto anticoagulation. Furthermore, hypercoagulability is now an increasingly recognized aspect of chronic liver disease (CLD), and the bleeding risk of VTE prophylaxis and treatment remains unclear. In this review, we provide an updated discussion on the mechanisms involved in hemostasis in CLD as well as on the benefits and complications of anticoagulant therapy in cirrhotic patients. Overall, sufficient evidence exists, promoting the use of anticoagulation in cirrhotic patients for both VTE prophylaxis and treatment in carefully selected patients after consideration of pharmacologic or endoscopic variceal bleeding prophylaxis.

Tocilizumab Promotes Regulatory T-cell Alleviation in STAT3 Gain-of-function-associated Multi-organ Autoimmune Syndrome.

PURPOSE: Signal transducer and activator of transcription 3 is a member of a family of proteins involved in the regulation of inflammation, differentiation, proliferation, and survival of cells. Here we describe a 38-year-old male who has experienced gastrointestinal, dermatologic, pulmonary, and malignant manifestations. METHODS: Whole-exome sequencing, validated by Sanger sequencing, was performed after extensive investigations. FINDINGS: Whole-exome sequencing revealed a heterozygous missense mutation in the signal transducer and activator of transcription 3 gene, c.1261G>A (p.G421R). Fluorescence-activated cell sorting analysis of peripheral T lymphocytes revealed low levels of CD4+CD25+FoxP3 and CD8+CD25+FoxP3 regulatory T cells. After treatment with 2 cycles of tocilizumab, an interleukin-6 receptor antibody, a significant increase in the level of regulatory T cells was observed, accompanied by clinical improvement. IMPLICATIONS: This case sheds light on the emerging role of signal transducer and activator of transcription 3 gain-of-function mutation in the pathogenesis of autoimmune diseases, and further addresses the therapeutic role of interleukin-6 blocker treatment in this syndrome.